Abstracts

This is a Late-Breaking abstract.

Rationale: Nearly 90% of tuberous sclerosis complex (TSC) patients have focal-onset epilepsy, and most are drug resistant. Cenobamate (CBM) is a novel antiseizure medication with proven efficacy in focal epilepsy treatment; however, there is a lack of information on its use in TSC patients. This study aims to assess the short-term efficacy of CBM in TSC patients with epilepsy.

Methods: We performed a retrospective chart review to identify TSC patients with epilepsy who received CBM at Cincinnati Children’s Hospital, U.S., from January 2021 until August 2022. Seizure frequency (parental report) at 1 month before CBM initiation was considered the baseline, and frequency 1- and 3-months post-initiation was collected. In addition, the family’s overall impression of seizure control and side effects were evaluated. Mean ±SD was used to report descriptive findings. Spearman’s rank correlation was used to evaluate the relationships between predictive factors and seizure outcomes.

Results: A total of 41 (14 female) patients aged 19.7 ±9.9 years were included. Past and concurrent antiseizure medications numbered 7.7 ±3.4 and 2.8 ±1.1, respectively. CBM was started at 18.6±9.8 years of age with a dose of 4.34±2.42 mg/kg/day and 233±126 mg/day. The family’s overall subjective impression indicated reduced seizure frequency or intensity in 29 (71%) patients and worsening seizures in 1 (2%). Improvements in behavior and sleep were seen in 2 patients, as was improved alertness (5%). Seizure numbers at 1-, 3-, and 6-mo post-CBM initiation were available in 29, 32, and 16 patients, respectively. After 1 mo of treatment, 19 (65.5%) patients had improvements with a mean seizure reduction of 59 (±29) %, while 6 (20.7%) had more seizures with a mean increase of 132 (±162) %. Four (13.8%) patients had unchanged seizure frequency. At 3 mo, 19 (59%) patients showed seizure reduction with a mean of 72.1 (±26.8) %, while 11 (34.3%) showed a mean of 185 (±177) % increased seizures, and 2(6.3%) were unchanged. At 6 mo, 12 (75%) patients showed improvements with a mean seizure reduction of 23 (±27) %. Seizures worsened in 2 (12.5%) patients and were unchanged in the other 2. Neither the age at treatment, age at seizure onset, dose/kg, or baseline seizure frequency correlated with the seizure outcomes. However, CBM dose/day approached a statistically significant correlation with seizure frequency change at 3 mo (Spearman r = 0.33, p = 0.053). Based on a robust regression, for each 100 mg increase in CBM daily dose, seizure frequency at 3 mo reduced by 0.14% (p = 0.066). Thirty (73%) patients reported side effects, with the most common being sedation (49%), behavioral disturbance (32%), GI issues (14%), and dizziness (5%). All except three patients continued cenobamate at the time of this study (93%).

Conclusions: Subjective and measurable improvements in seizures were seen in the short-term follow-up in most patients. While side effects were common, nearly all patients continued the treatment indicating good tolerability. These findings suggest potential values of CBM in TSC patients with epilepsy. 

Funding: None